Metabolic and toxic brain injury

Lesion

Low sugar, ammonia from a failing liver and poisons such as carbon monoxide, alcohol and methanol each damage particular parts of the brain.

Updated Nov 12, 2026

Key points

Hypoglycemia: large cortical pyramidal neurons and hippocampal neurons (including dentate gyrus) die; Purkinje cells are relatively spared, unlike in hypoxia.
Hepatic encephalopathy: Alzheimer type II astrocytes in cortex and basal ganglia; ammonia impairs astrocyte function; asterixis and confusion.
Carbon monoxide: binds hemoglobin tightly; bilateral necrosis of the globus pallidus, and delayed white matter damage.
Chronic alcohol: atrophy of the anterior superior cerebellar vermis with truncal ataxia; also Wernicke-Korsakoff, central pontine myelinolysis and Marchiafava-Bignami disease.
Methanol: metabolised to formic acid; retinal ganglion cell death causes blindness, with putaminal necrosis.
Radiation necrosis: delayed fibrinoid necrosis of vessels and coagulative necrosis of white matter, months to years after treatment.

What it is

The brain depends on a constant supply of glucose and oxygen and is exposed to anything that crosses the blood-brain barrier. Severe hypoglycemia kills neurons much like hypoxia does. Liver failure lets ammonia reach the brain, where astrocytes swell and change. Toxins have favourite targets: carbon monoxide the globus pallidus, chronic ethanol the anterior cerebellar vermis, methanol the retina and putamen. Therapeutic radiation can cause delayed necrosis of white matter.

Step by step

A substrate is missing (glucose) or a toxin reaches the brain (ammonia, carbon monoxide, alcohols).
Neurons or glia with the highest exposure or need are hit first.
Astrocytes swell and fail when ammonia is detoxified into glutamine inside them.
Energy failure, oxidative stress and excitotoxicity kill vulnerable cells.
Lesions take the pattern of the cell type and region most affected.

Metabolic and toxic insults and their targets

Insult	Favourite target	Clue
Severe hypoglycemia	Cerebral cortex, hippocampus	Neuronal necrosis, Purkinje cells spared
Hyperammonemia (liver failure)	Astrocytes throughout grey matter	Alzheimer type II astrocytes, asterixis
Carbon monoxide	Globus pallidus, white matter	Cherry-red skin, delayed leukoencephalopathy
Chronic ethanol	Anterior cerebellar vermis	Truncal ataxia, wide-based gait
Methanol	Retina, putamen	Blindness, high anion gap acidosis
Lead (children)	Brain capillaries	Edema, encephalopathy, developmental loss
Radiation	White matter and vessels	Delayed necrosis, mimics tumour recurrence

Clinical notes

Metabolic encephalopathies are often reversible if the cause is corrected early; structural damage is not.
Methanol poisoning outbreaks from adulterated alcohol occur in Latin America and need urgent recognition.

Test yourself

Think of the answer, then tap the question to see it.

Which brain structure is characteristically necrotic after carbon monoxide poisoning?

The globus pallidus, on both sides.

What astrocytic change marks hepatic encephalopathy?

Alzheimer type II astrocytes, with enlarged pale nuclei, from hyperammonemia.

Why does methanol cause blindness?

It is metabolised to formic acid, which poisons mitochondria of retinal ganglion cells and the optic nerve.

Add to my cards (3)

Elsewhere in DurgiPedia

Carbon monoxide, methemoglobin and cyanide

Connections

← All of general pathology

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: Loss of brain function - liver disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Carbon monoxide poisoning: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Methanol poisoning: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.